Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells

Authors: Lenka V. Hurton, Harjeet Singh, Amer Najjar, Kirsten C. Switzer, Tiejuan Mi, Sourindra N. Maiti, Simon Olivares, Brian Rabinovich, Helen Huls, Marie-Andrée Forget, Vrushali Datar, Partow Kebriaei, Dean A. Lee, Richard E. Champlin, Laurence J.N. Cooper - Proceedings of the National Academy of Sciences, PNAS 2016 cited by 458

Significance We describe an approach based on cytokine therapeutics to enhance the persistence and effectiveness of T-cell–based immunotherapies using chimeric antigen receptors (CARs). This strategy is effective without the use of high-dose exogenous cytokines that are typically associated with toxicities. Moreover, we report that the persistence of the least differentiated memory T cell, the T-memory stem cell, was promoted by signaling induced by a membrane-bound chimeric IL-15 cytokine-fusion molecule. These findings may contribute to improving the safety and therapeutic efficacy of CAR-based immunotherapies of patients with advanced cancer.